Is RAB3GAP1 p.Asp137= (c.411C>T) pathogenic?

RAB3GAP1 p.Asp137= (c.411C>T) is classified Conflicting classifications of pathogenicity in RAB3GAP1 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-06-01). Low-frequency (popmax 1.55%, mid); Associated with Warburg micro syndrome 1.

What condition is associated with RAB3GAP1 p.Asp137= (c.411C>T)?

RAB3GAP1 p.Asp137= (c.411C>T) is associated with Warburg micro syndrome 1 (ClinVar).

How common is RAB3GAP1 p.Asp137= (c.411C>T) in the general population?

RAB3GAP1 p.Asp137= (c.411C>T) is low-frequency (popmax 1.55%, mid) (gnomAD).

RAB3GAP1 p.Asp137=

c.411C>T · rs140929274 · VCV331121

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.55%, mid)

Conditions

Warburg micro syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.096	GERP -3.4, phastCons 0.86
Overall
CADD	11.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.55% Middle Eastern · 94/6,062 alleles

Filtering AF 1.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2%

Overall 0.0626% 1,010/1,614,056 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.55%	64
Ashkenazi Jewishnot grpmax-eligible	0.213%	470
Remaining individualsnot grpmax-eligible	0.12%	833
Admixed American	0.0683%	1,464
South Asian	0.0659%	1,518
European (non-Finnish)	0.0551%	1,815
African / African-American	0.0333%	3,001
Finnishnot grpmax-eligible	0.00312%	32,015

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: RAB3GAP1
Protein: p.Asp137=
Coding: c.411C>T
MANE Select: NM_012233
dbSNP: rs140929274
Type: single nucleotide variant
Location: chr2:135113199 (GRCh38)
Gene constraint: LOEUF 0.798 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.46 · 1 PDB

Full RAB3GAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Warburg micro syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RAB3GAP1 c.2607-1G>C Pathogenic ★★ same condition
RAB3GAP1 c.748+1G>A Pathogenic ★★ same condition
RAB3GAP1 c.899+1G>A Pathogenic ★★ same condition
RAB3GAP1 p.Arg187Ter Pathogenic ★★ same condition
RAB3GAP1 p.Arg337Ter Pathogenic/Likely pathogenic ★★ same condition
RAB3GAP1 p.Arg347Ter Pathogenic ★★ same condition
RAB3GAP1 p.Arg392Ter Pathogenic ★★ same condition
RAB3GAP1 p.Gln246Ter Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/rab3gap1-p-asp137 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown